The resistance of microorganisms to antimicrobial agents remains a pressing problem that poses a threat to human life. Among the important factors contributing to the spread of antibiotic-resistant strains of bacteria is the formation of biofilms. They are the cause of chronic recurrent infections (about 80 %) and ineffectiveness of antibiotic therapy. One way to solve this problem is search for new substances, which able to disrupt the different stages of biofilm formation. The dissertation is devoted to the study of the antibiofilm activity features of new derivatives of 4-(1'-adamantyl)-1R-benzene against gram-positive and gram-negative bacteria (methicillin-resistant S. aureus(MRSA), E. coli, P. aeruginosa), which are included in the list of priorities microorganisms for the creation of antimicrobial agents. The studies used 2 compounds: 4-(adamantyl-1)-1-(1-aminobutyl) benzene (code AM-166) and 1-[4-(1-adamantyl)-phenoxy]-3-(N-benzyl,N-dimethylamino)-2-propanol chloride (code KVM-97). In vitro experiments have shown that 4-(1'-adamantyl)-1R-benzene derivatives exhibit antibiofilm activity at the first stages of biofilm formation. Under their action at sub-MIC and at concentrations exceeding 1.0 MIC a decrease in the biomass of biofilms (in the range from 22.5 % to 92.3 %) and the number of metabolically active cells MRSA, E. coli, P. аeruginosa was found. Derivatives of 4-(1'-adamantyl)-1R-benzene affect nonspecific (the cell hydrophobicity of the MRSA (AM-166), P. aeruginosa (KVM-97)) and specific adhesion factors of microorganisms (twitching-migration of E. coli and P. aeruginosa). The compounds AM-166 and KVM-97 do not disrupt the formation of persister cells of S. aureus, P. aeruginosa and reduce the persisters formation of E. coli. The persister cells of P. aeruginosa are susceptible to AM-166 and KVM-97. The effectiveness of 0.05 % KVM-97 solution was proven in in vivo studies on a model of surgical skin wound in rats infected with mixed pathogens (S. aureus + P. aeruginosa + C. albicans), a reduction in microbial contamination on the surface and in the depth of the wound was note. The antimicrobial activity of 4-(1’-adamantyl)-1R-benzene derivatives is observed when applied to a polypropylene surgical mesh for reconstructive surgery, that a more pronounced against MSSA, MRSA, C. albicans. The compounds AM-166 and KVM-97 cause the destruction of formed biofilms, under their action a decrease in the biomass of 2-day MRSA biofilms, 5-day E. coli and P. aeruginosa biofilms was observed. It was showed that 4-(1’-adamantyl)-1R-benzene derivatives penetrate the matrix of the biofilm formed by MRSA and practically do not affect its components. The studied compounds characterized by limited penetration through the matrix of biofilms of E. coli and P. аeruginosa. Under their action, a changes in the amount of protein and polysaccharide components of the extracellular matrix were detected. The obtained molecular research data indicate that 4-(1’-adamantyl)-1R-benzene derivatives (0.5 MIC) change the expression of biofilm-forming genes. Under their action a decrease in the expression of the genes of the icaADBC operon, genes regulating the synthesis of surface adhesin proteins (clfB, fib, finbB, ebpS, eno), the release of eDNA and the Quorum sensing (QS) system (cidA and agrA only KVM-97), an increase in the activity of the regulatory gene icaR in MRSA was note. The compounds cause genomic variability in S. aureus. It was found that the AM-166 and KVM-97 affects the expression of genes appB, appX and malP, malZ (KVM-97), that regulate energy processes in E. coli, genes fliC, motB, fimA (AM-166), that ensure the motility of E. coli and adhesion of cells to the substrate. It was established that adamantane-containing compounds change the transcriptional activity of genes that regulate the synthesis of polysaccharide components of the matrix Pel, Psl, alginate (pelA, pslA, algD, algL, algR, algU, mucA) in P. aeruginosa. Under their action both stimulation and inhibition of the expression of the studied genes are note. It was showed that 4-(1’-adamantyl)-1R-benzene derivatives at sub-MIC affect the functioning of QS (reduce the expression of the lasI, lasR, pqsR genes, increase – gene rhlR) and QS-dependent processes (reduce the expression of the aprA, exoS, exoA genes, lead to violated of the production of pyocyanin and hemolytic activity) in P. aeruginosa. Under the action of the compounds change the transcriptional activity of the genes of efflux pumps of the RND family (mexB, mexY, oprM, mexR) are observed. Thus, 4-(1’-adamantyl)-1R-benzene derivatives exhibit antibiofilm activity, which is more pronounced at the initial stages of biofilm formation, that was confirmed by in vitro and in vivo experiments. Their action is realized by influencing cell hydrophobicity, migration, expression of genes that regulate biofilm formation, energy processes, exopolysaccharide synthesis, functioning of efflux pumps and
